Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval, Quebec City, QC, G1V 0A6, Canada.
Department of Medicine, Laval University, Quebec City, QC, G1V 0A6, Canada.
Commun Biol. 2020 Aug 28;3(1):477. doi: 10.1038/s42003-020-01210-x.
Calcific aortic valve stenosis (CAVS) is a frequent heart disease with significant morbidity and mortality. Recent genomic studies have identified a locus near the gene PALMD (palmdelphin) strongly associated with CAVS. Here, we show that genetically-determined expression of PALMD in the aortic valve is inversely associated with CAVS, with a stronger effect in women, in a meta-analysis of two large cohorts totaling 2359 cases and 350,060 controls. We further demonstrate the specificity of this relationship by showing the absence of other significant association between the genetically-determined expression of PALMD in 9 tissues and 852 phenotypes. Using genome-wide association studies meta-analyses of cardiovascular traits, we identify a significant colocalized positive association between genetically-determined expression of PALMD in four non-cardiac tissues (brain anterior cingulate cortex, esophagus muscularis, tibial nerve and subcutaneous adipose tissue) and atrial fibrillation. The present work further establishes PALMD as a promising molecular target for CAVS.
钙化性主动脉瓣狭窄（CAVS）是一种常见的心脏病，具有显著的发病率和死亡率。最近的基因组研究已经确定了一个位于基因 PALMD（palmdelphin）附近的位点，与 CAVS 强烈相关。在这里，我们通过对两个大型队列的荟萃分析表明，主动脉瓣中基因决定的 PALMD 表达与 CAVS 呈负相关，在女性中作用更强，该队列共有 2359 例病例和 350060 例对照。我们通过显示 PALMD 在 9 种组织和 852 种表型中的基因决定表达之间不存在其他显著关联，进一步证明了这种关系的特异性。通过对心血管特征的全基因组关联研究荟萃分析，我们在四个非心脏组织（大脑前扣带回皮质、食管肌肉层、胫骨神经和皮下脂肪组织）和心房颤动中发现了基因决定的 PALMD 表达之间存在显著的阳性关联。本工作进一步确立了 PALMD 作为 CAVS 的有前途的分子靶点。
